The relationship of histocompatibility antigens and immune reactivity to autoimmunity and longevity will be studied prospectively in aged human subjects. Elderly humans will be evaluated for cellular and humoral immune reactivity and grouped into classes with low, intermediate and high immune reactivity. The histocompatibility phenotype of the elderly persons studied will be determined. The subjects of this study will be followed for a 5-year period for the occurrence of autoimmune phenomena (appearance of antinuclear antibody, rheumatoid factor, etc.) and survival. The survival value of immune reactivity and histocompatibility phenotype will be assessed. The nature of the immunologic defect observed in aging mice and humans will be studied. The impaired proliferative capacity of lymphocytes from aged humans will be studied in vitro with particular regard to the reported decline in serum thymosin concentration with age. The defect in antibody response after immunization will be studied in young and aged mice using cell transfer techniques to identify the cellular basis of this immune defect.